1,2-dichloro-4-nitrobenzene

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Documentation suffers from deficiencies mainly because of limited documentation.

Data source

Reference

Reference Type:

publication

Title:

Hygienic standard for 3,4-dichloronitrobenzene vapor in the air of working premises.

Author:

Belyaev VA and Kuznetsov AV

Year:

1969

Bibliographic source:

Hyg Sanit 34: 211 - 214

Materials and methods

Principles of method if other than guideline:

Method: other: see freetext ME

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

m/p Cresol

IUPAC Name:

m/p Cresol

Details on test material:

IUCLID4 Test substance: other TS: 1,2-dichloro-4-nitrobenzene, no data on purity but melting point: 43°C

Test animals

Species:

other: rats or mice

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

other: migrated dataset

Vehicle:

other: migrated dataset

Remarks on MMAD:

MMAD / GSD: migrated dataset

Duration of treatment / exposure:

4 months

Frequency of treatment:

4 hrs/d

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.4, 3.6, 10 mg/m3
Basis:

Control animals:

yes

Details on study design:

Post-exposure period: no data

Results and discussion

Effect levels

Dose descriptor:

NOAEC

Effect level:

0.4 mg/m³ air

Sex:

not specified

Basis for effect level:

other: based on significant changes in the hematological parameters from 3.6 mg/m³ onwards including methemoglobinemia and Heinz bodies

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

RS-Freetext:
RATS and MICE : 
No effects on behaviour and body weights.
RATS and MICE: 
Blood counts and biochemical tests revealed significant changes, 
mainly  among animals treated with a concentration of 10 mg/m³
e.g. RATS: 
0.4 mg/m3: 
no adverse effects were reported;
3.6 mg/m3: 
increase in Heinz bodies (up to 7 %) and
reticulocytes (up to 19.6 %); 
significantly increased activity of liver catalase 
(35.6 versus 26.5[catalase numbers] of control);
10 mg/m3: 
significant changes in blood counts and biochemical tests:  
decrease in  RBC of 10% towards the 18th day  of treatment, 
decreased haemoglobin  levels from 15.1g% to 12.2 g%, 
neutrophilic leucocytosis, pronounced  reticulocytosis, 
increase in Heinz bodies and in methaemoglobin levels  (up to 7.6 %); 
significantly (sig.) increased activities of serum transaminases  
(Glutamic-alanine-transa.: 35.4 versus 28.9 [extinction units] of  controls; 
Glutamatic-aspartic-transa.: 141.5 versus 121.8 [extinction  units] of controls), 
sig. liver catalase (47.6 versus 26.5 [cataslase  numbers] of controls), 
sig. liver  diaminooxidase (56.8 versus 41.4 [ug/g  tissue] of controls), 
sig. increased levels of bilirubin in blood (6.03  versus 2.0 [mg%] of controls),
 sig. increased cholesterol level in  adrenals (4.7 versus 3.7 [mg/100 g tissue] of controls); 
histological examination:
10 mg/m³: morphological changes of the brain 
(cells with hyperchromic  nuclei most commonly in the subcortical ganglia).

Applicant's summary and conclusion

Executive summary:

Inhalation exposure of rats for 4 months against 0.4 to 10 mg/m³ 1,2 -dichloro-4-nitrobenzene yielded a NOAEC of 0.4 mg/m³ based on significant changes in the hematological parameters from 3.6 mg/m³ onwards including methemoglobinemia and Heinz bodies